Copper(II) and Zinc(II) complexes of new water-soluble Schiff base ligands and their antiproliferative properties towards mesothelioma cell line

In this work, three Schiff base ligands (HL¹-HL³) containing a triphenyl phosphonium cation and their Cu(II) and Zn(II) complexes with the general formulae of [M(L)Cl₂] were synthesized and their structures were characterized by spectroscopic and analytical methods. Crystal structure of complex [Zn(L¹)Cl₂] was determined. In the structure of the complex, each Zn(II) ion is four coordinated binding to phenolate oxygen and imine nitrogen atoms of the ligand L¹ and two chloride atoms in approximately tetrahedral geometry. The equilibrium geometry of three Schiff base ligands (HL¹-HL³) and their Cu(II) and Zn(II) complexes were calculated using the density functional theory (DFT/B3LYP) method with the 6–31++G(d,p) basis set for the C, H, Cl, N, O, P atoms and LANL2DZ for the I atom. Frontier molecular orbitals (HOMO, LUMO) analyses were conducted for the optimized geometries of the compounds, and chemical reactivity descriptors such as hardness, softness, electrophilicity, and electronegativity were examined. Additionally, the molecular electrostatic potential (MEP) of all compounds was modeled using DFT calculations. These calculations were thoroughly examined, and their implications were discussed. The ligands and their metal complexes were investigated for their DNA binding properties. The compounds showed comparable DNA binding properties to ethidium bromide (EB) and 5-fluorouracyl (5-Fu) with DNA binding constant (K_b) 1.5–6.25 × 10⁵ M⁻¹. The cytotoxic properties of the compounds towards HUVEC and H2452 (mesothelioma cell line) cells were investigated using an MTS assay. The IC₅₀ values determined for HUVEC cells were found to range between 27.28 µg/mL ([Cu(L²)Cl₂]) and 273.1 µg/mL ([Zn(L²)Cl₂]), while in H2452 cells, they varied from 39.48 µg/mL ([Cu(L²)Cl₂]) to 319.3 µg/mL ([Zn(L³)Cl₂]). The compounds HL¹, HL³, and [Zn(L³)Cl₂] exhibited antioxidant activity at the highest concentration (750 µg/mL) only, while [Zn(L¹)Cl₂], HL², [Zn(L²)Cl₂], [Cu(L²)Cl₂], and [Cu(L³)Cl₂] showed antioxidant activity at 250 µg/mL.